Several factors having chemotactic properties to monocytes are known. Among these, monocyte chemotactic and activating factor (hereinafter referred to as "MCAF") also known as MCP-1 (monocyte chemoattractant protein-1) or GDCF (glioma-derived monocyte chemotactic factor), is a protein consisting of 76 amino acids, which has 4 cysteine residues. It is known that this protein has a strong chemotactic activity to monocytes and a strong monocyte-activating property.
Identification and gene cloning of MCAF, MCP-1 and GDCF are described in the following references:
1) K. Matsushima et al., J. Exp. Med., 169, 1485-1490, 1989; PA1 2) Y. Furutani et al., Biochem. Biophys. Res. Commun., 159, 249-255, 1989; PA1 3) E. A. Robinson et al., Proc. Natl. Acad. Sci. USA, 86, 1850-1854, 1989; and PA1 4) T. Yoshimura et al., FEBS Letters, 244, 487-493, 1989. PA1 5) N. Mukaida et al., Microbiol. Immunol. 36, 773-789, 1992. PA1 6) T. A. Mastoe et al., J. Clin. Invest., 87, 694-703 (1991) .
General descriptions of the protein are described in the following reference:
MCP-1 and GDCF described in the References 3) and 4) are the same substance as MCAF, described in the References 1) and 2).
It is known that MCAF strongly attracts and activates monocytes, and uses exploiting immunopotentiation and anti-tumor properties are suggested in the above-mentioned references. Further, as a general concept, it is known that monocytes which have gathered in a wound play a role in the natural healing of the wound. However, it is not known that MCAF has an activity to directly promote therapy of wounds.
It is known that several proteinous growth factors promote healing of wounds. For example, growth factors such as fibroblast growth factor (FGF), epidermal growth factor (EGF), transforming growth factor (TGF-.alpha., TGF-.beta.), platelet-derived growth factor (PDGF), endothelial cell growth factor (ECGF) and keratinocyte growth factor are expected to have therapeutic activities for wounds (Reference 6).
It was recently reported in U.S. Pat. No. 5,202,118 that interleukin-1 (IL-1) has a therapeutic effect for wounds.